Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant disease of swine worldwide. It is characterized by late term reproductive failure in sows and severe pneumonia in neonatal pigs. The etiologic agent of PRRS, the PRRS virus (PRRSV), is a small, enveloped virus containing a single positive-stranded RNA genome. PRRSV is a member of the family Arteriviridae, in the order Nidovirales. The Arteriviridae family also includes equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV).
PRRSV can be divided into two major genotypes; Type I (also referred to as European genotype) and Type II (also referred to as North American genotype). Highly pathogenic variants (HP-PRRSV) that recently emerged in China and other Asian countries are originated from a virus of type II genotype.
The PRRSV genome is about 15 kb in length and contains at least ten open reading frames. The 3′ end of the genome encodes four membrane-associated glycoproteins (GP2a, GP3, GP4 and GP5; expressed from sg mRNAs 2-5), three unglycosylated membrane proteins (E, ORF5a and M; expressed from sg mRNAs 2, 5 and 6) and a nucleocapsid protein (N; expressed from sg mRNA 7) (de Boon et al., 1991; Meulenberg et al., 1993, 1995; Snijder et al., 1999; Wu et al., 2001, 2005; Firth et al., 2011; Johnson et al., 2011).
The PRRSV replicase genes, ORF1a and ORF1b, situated in the 5′-proximal of the genome, represent nearly 75% of the viral genome. ORF1a and ORF1b encode two long replicase polyproteins, pp1a and the pp1ab, which are proteolytically processed into (at least) 14 nonstructural protein (nsp) products (Ziebuhr et al., 2000; Fang and Snijder, 2010). Of these, nsp2 is the largest cleavage product, which is released by the autoproteolytic activity of the upstream nsp1β towards the nsp1β/2 site and the cleavage of the nsp2/3 site by a papain-like protease, PLP2, residing in the N-terminal domain of nsp2 (Snijder et al., 1995).
Presently, there is no effective treatment or vaccine for combating or preventing PRRSV infection. The impact of PRRS is approximately $600 million in losses each year to the U.S. swine industry alone, and several times this amount worldwide. Basic knowledge, antiviral strategies, and tools are needed to reduce animal suffering, as well as economic losses to producers and society through the control and/or elimination of PRRS.